The affected-pedigree-member method of linkage analysis.
The affected-pedigree-member method of linkage analysis.
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DOI：
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发表时间：
1988-02
影响因子：
9.8
通讯作者：
D. Weeks;K. Lange
中科院分区：
文献类型：
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作者：
D. Weeks;K. Lange
本文将连锁分析的影响同胞对方法推广到家系。通过用身份-状态关系代替身份-血统关系，我们开发了一个检验统计量，用于检测疾病和标记表型的独立分离偏离。该统计仅基于受影响谱系成员的标记表型。由于远距离受影响的亲属共享一个罕见的标记等位基因比共享一个共同的标记等位基因更引人注目，因此统计数据还包括基于等位基因频率的加权因子。统计量的分布特性进行了理论研究和模拟。部分的理论治疗需要概括Karigl的多人亲属系数。当检验统计量应用于亨廷顿病的系谱数据时，标记基因座和疾病基因座之间独立分离的零假设被坚决拒绝。在这种情况下，正如预期的那样，与标准lod评分分析相比，功效有所损失。然而，我们的统计数据具有不需要明确假设疾病的遗传方式的优势。这一点是说明了应用程序的测试统计数据类风湿关节炎。
This paper describes a generalization of the affected-sib-pair method of linkage analysis to pedigrees. By substituting identity-by-state relations for identity-by-descent relations, we develop a test statistic for detecting departures from independent segregation of disease and marker phenotypes. The statistic is based on the marker phenotypes of affected pedigree members only. Since it is more striking for distantly affected relatives to share a rare marker allele than a common marker allele, the statistic also includes a weighting factor based on allele frequency. The distributional properties of the statistic are investigated theoretically and by simulation. Part of the theoretical treatment entails generalizing Karigl's multiple-person kinship coefficients. When the test statistic is applied to pedigree data on Huntington disease, the null hypothesis of independent segregation between the marker locus and the disease locus is firmly rejected. In this case, as expected, there is a loss of power when compared with standard lod-score analysis. However, our statistic possesses the advantage of requiring no explicit assumptions about the mode of inheritance of the disease. This point is illustrated by application of the test statistic to data on rheumatoid arthritis.